Hormonal changes in the menopause transition.
01 Jan 2002-Recent Progress in Hormone Research (RECENT PROGRESS IN HORMONE RESEARCH)-Vol. 57, Iss: 1, pp 257-275
TL;DR: Symptoms of the menopause can be interpreted as resulting primarily from the profound fall in estradiol, occurring over a 3- to 4-year period around final menses, a fall that presumably contributes importantly to the beginning, in the late perimenopause, of loss of bone mineral density.
Abstract: The menopause is the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. It is heralded by the menopausal transition, a period when the endocrine, biological, and clinical features of approaching menopause begin. A common initial marker is the onset of menstrual irregularity. The biology underlying the transition to menopause includes central neuroendocrine changes as well as changes within the ovary, the most striking of which is a profound decline in follicle numbers. Follicle-stimulating hormone (FSH) is an established indirect marker of follicular activity. In studies of groups of women, its concentration, particularly in the early follicular phase of the menstrual cycle, begins to increase some years before there are any clinical indications of approaching menopause. The rise in FSH is the result of declining levels of inhibin B (INH-B), a dimeric protein that reflects the fall in ovarian follicle numbers, with or without any change in the ability of the lining granulosa cells to secrete INH-B. Estradiol levels remain relatively unchanged or tend to rise with age until the onset of the transition and are usually well preserved until the late perimenopause, presumably in response to the elevated FSH levels. During the transition, hormone levels frequently vary markedly - hence, measures of FSH and estradiol are unreliable guides to menopausal status. Concentrations of testosterone have been reported to fall by about 50% during reproductive life, between the ages of 20 and 40. They change little during the transition and, after menopause, may even rise. Dehydroepiandrosterone (DHEA) and DHEAS, its sulphate, on the other hand, decline with age, without any specific influence of the menopause. Symptoms of the menopause can be interpreted as resulting primarily from the profound fall in estradiol, occurring over a 3- to 4-year period around final menses, a fall that presumably contributes importantly to the beginning, in the late perimenopause, of loss of bone mineral density.
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TL;DR: The features of the metabolic syndrome that emerge with estrogen deficiency are reviewed to aid in the recognition and treatment of women at risk for future CVD, leading to appropriate interventions.
Abstract: Women with the metabolic syndrome (central obesity, insulin resistance, and dyslipidemia) are known to be at especially high risk for cardiovascular disease (CVD). The prevalence of the metabolic syndrome increases with menopause and may partially explain the apparent acceleration in CVD after menopause. The transition from pre- to postmenopause is associated with the emergence of many features of the metabolic syndrome, including 1) increased central (intraabdominal) body fat; 2) a shift toward a more atherogenic lipid profile, with increased low density lipoprotein and triglycerides levels, reduced high density lipoprotein, and small, dense low density lipoprotein particles; 3) and increased glucose and insulin levels. The emergence of these risk factors may be a direct result of ovarian failure or, alternatively, an indirect result of the metabolic consequences of central fat redistribution with estrogen deficiency. It is unclear whether the transition to menopause increases CVD risk in all women or only those who develop features of the metabolic syndrome. This article will review the features of the metabolic syndrome that emerge with estrogen deficiency. A better understanding of these metabolic changes with menopause will aid in the recognition and treatment of women at risk for future CVD, leading to appropriate interventions. (J Clin Endocrinol Metab 88: 2404 –2411, 2003)
1,254 citations
Cites background from "Hormonal changes in the menopause t..."
...Menstrual history is the most reliable indicator of the postmenopausal state, as specific hormonal measures, such as estradiol (E2) and FSH levels both vary widely in the perimenopause during an individual menstrual cycle (2)....
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...Although it is commonly believed that E2 levels fall gradually throughout the perimenopause, concentrations are preserved until relatively late in the perimenopausal period, as E2 does not decline significantly until women experience at least 3 months of amenorrhea (2)....
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TL;DR: It is revealed that a substantial proportion of the old people has sarcopenia, even in healthy populations, and early diagnosis can prevent some adverse outcomes.
Abstract: Sarcopenia, an age-related decline in muscle mass and function, is one of the most important health problems in elderly with a high rate of adverse outcomes. However, several studies have investigated the prevalence of sarcopenia in the world, the results have been inconsistent. The current systematic review and meta- analysis study was conducted to estimate the overall prevalence of sarcopenia in both genders in different regions of the world. Electronic databases, including MEDLINE (via PubMed), SCOPUS and Web of Science were searched between January 2009 and December 2016. The population- based studies that reported the prevalence of sarcopenia in healthy adults aged ≥ 60 years using the European Working Group on Sarcopenia in Older People (EWGSOP), the International Working Group on Sarcopenia (IWGS) and Asian Working Group for Sarcopenia (AWGS) definitions, were selected. According to these consensual definitions, sarcopenia was defined by presence of low muscle mass (adjusted appendicular muscle mass for height) and muscle strength (handgrip strength) or physical performance (the usual gait speed). The random effect model was used for estimation the prevalence of sarcopenia. The sex-specific prevalence of sarcopenia and 95% confidence interval (CI) were calculated using the Binomial Exact Method. Heterogeneity was assessed by subgroup analysis. Thirty- five articles met our inclusion criteria, with a total of 58404 individuals. The overall estimates of prevalence was 10% (95% CI: 8-12%) in men and 10% (95% CI: 8-13%) in women, respectively. The prevalence was higher among non- Asian than Asian individuals in both genders especially, when the Bio-electrical Impedance Analysis (BIA) was used to measure muscle mass (19% vs 10% in men; 20% vs 11% in women). Despite the differences encountered between the studies, regarding diagnostic tools used to measure of muscle mass and different regions of the world for estimating parameters of sarcopenia, present systematic review revealed that a substantial proportion of the old people has sarcopenia, even in healthy populations. However, sarcopenia is as a consequence of the aging progress, early diagnosis can prevent some adverse outcomes.
582 citations
Cites background from "Hormonal changes in the menopause t..."
...After menopausal transition, the concentrations of sex steroids, both estrogens and androgens, decrease dramatically [17]....
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Trinity University1, University of California, Davis2, California National Primate Research Center3, Wake Forest University4, Biomedical Primate Research Centre5, Georgia State University6, Yerkes National Primate Research Center7, University of Washington8, University of Texas Health Science Center at San Antonio9, Baylor College of Medicine10, University of Wisconsin-Madison11
TL;DR: Key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research are reviewed.
Abstract: Research involving nonhuman primates (NHPs) has played a vital role in many of the medical and scientific advances of the past century. NHPs are used because of their similarity to humans in physiology, neuroanatomy, reproduction, development, cognition, and social complexity-yet it is these very similarities that make the use of NHPs in biomedical research a considered decision. As primate researchers, we feel an obligation and responsibility to present the facts concerning why primates are used in various areas of biomedical research. Recent decisions in the United States, including the phasing out of chimpanzees in research by the National Institutes of Health and the pending closure of the New England Primate Research Center, illustrate to us the critical importance of conveying why continued research with primates is needed. Here, we review key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research.
442 citations
Cites background from "Hormonal changes in the menopause t..."
...As in women [Burger et al., 2002], estradiol concentrations and cycle length becomes irregular [Downs & Urbanski, 2006; Gilardi et al., 1997; Gore et al., 2004; Hodgen et al., 1977; Shideler et al., 2001] with extended follicular phases [Gilardi et al., 1997]....
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...As in women [Burger et al., 2002], estradiol concentrations and cycle length becomes...
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TL;DR: It is suggested that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR 1 could be considered a quantitative trait locus.
Abstract: BACKGROUND: Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk. METHODS: Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes. RESULTS AND CONCLUSIONS: We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (≥ 100 repeats).
411 citations
Cites background from "Hormonal changes in the menopause t..."
...Perhaps obtaining only one measure of FSH is not sensitive enough to detect a difference among women who may be in menopause transition (Burger et al., 2002)....
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TL;DR: The data indicate complex interactions between age, APOE genotype and gender that belies a one size fits all approach and argues for a precision medicine approach that integrates across the three main risk factors for Alzheimer's disease.
363 citations
References
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TL;DR: The relationship between menopause transitions and symptom reporting appears to be transitory, with reported rates showing an increase in the perimenopause and a compensatory decrease in the postmenopause.
997 citations
TL;DR: Using this immunoassay, it was found that the plasma concentration of inhibin B rose rapidly in the early follicular phase to a peak of 85.2 +/- 9.6 pg/mL on the day after the intercycle FSH rise, then fell progressively during the remainder of the follicular phases, which suggests that these forms may have different physiological roles.
Abstract: This report describes the development of a specific and sensitive assay for inhibin B and its application to the measurement of inhibin B concentrations in plasma during the human menstrual cycle. A monoclonal antibody raised against a synthetic peptide from the betaB-subunit was combined with an antibody to an inhibin alpha-subunit sequence in a double antibody enzyme-linked immunosorbent assay format. The validated assay had a limit of detection of 10 pg/mL and 0.5% cross-reactivity with inhibin A. Using this immunoassay, we found that the plasma concentration of inhibin B rose rapidly in the early follicular phase to a peak of 85.2 +/- 9.6 pg/mL on the day after the intercycle FSH rise, then fell progressively during the remainder of the follicular phase. Two days after the midcycle LH peak, there was a short lived peak in the inhibin B concentration (133.6 +/- 31.2 pg/mL), which then fell to a low concentration (<20 pg/mL) for the remainder of the luteal phase. In contrast, the inhibin A concentration...
909 citations
"Hormonal changes in the menopause t..." refers background in this paper
...…of folliclestimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) during the normal menstrual cycle have been well known for several decades, it is only within the last 10 years that the changes in circulating inhibins have been documented (Groome et al., 1996)....
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...Although the changes that occur in the circulating concentrations of folliclestimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) during the normal menstrual cycle have been well known for several decades, it is only within the last 10 years that the changes in circulating inhibins have been documented (Groome et al., 1996)....
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...INH-B, on the other hand, is a secretory product of small antral follicles (Roberts et al., 1993; Groome et al., 1996)....
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...particularly from the dominant follicle and the ensuing corpus luteum (Roberts et al., 1993; Groome et al., 1996)....
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...INH-A, together with E2, is derived particularly from the dominant follicle and the ensuing corpus luteum (Roberts et al., 1993; Groome et al., 1996)....
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TL;DR: The mean number of primordial follicles in the ovaries of women who were still menstruating regularly was 10-fold higher than that in perimenopausal women, and follicles were virtually absent in the postmenopausal ovaries.
Abstract: Although the menopause is generally considered to be the consequence of follicular exhaustion, the relationship between follicle number and the menopausal transition has not been explicity studied. We addressed this question in 17 women, aged 45-55 yr, who were undergoing elective total abdominal hysterectomy and salpingo-oophorectomy. The women were divided into 3 groups according to their menstrual history: 1) menstruating regularly (n = 6), 2) perimenopausal (irregular menses; n = 7), and 3) postmenopausal (greater than 1 yr since last menses; n = 4). The mean ages of the 3 groups were similar. Menstrual histories were confirmed by plasma hormone levels and endometrial histology. One ovary from each woman was serially sectioned for determination of follicle numbers. The mean number of primordial follicles in the ovaries of women who were still menstruating regularly was 10-fold higher than that in perimenopausal women [1392 +/- 355 (+/- SEM) vs. 142 +/- 72]. Follicles were virtually absent in the postmenopausal ovaries. Comparison of these data with those obtained by others in younger women suggests that follicular depletion accelerates dramatically in the last decade of menstrual life. These results support the view that declining follicular reserve is the immediate cause of both the perimenopausal and menopausal transitions, and indicate that the rate and, therefore, the regulation of follicular depletion change during the final phase of reproductive life.
635 citations
TL;DR: The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.
Abstract: Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.
579 citations
"Hormonal changes in the menopause t..." refers background in this paper
...In some instances, they have been recorded as a function of age with little attention to menstrual cycle status (Sherman et al., 1976)....
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TL;DR: This study provides characterization of the menstrual pattern of the normal woman in terms of hormonal changes which occur and provides a basis of comparison for the detection of various disorders of follicular maturation.
Abstract: The changes in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FHS), estradiol, and progesterone that occur both early and late in reproductive life were characterized and compared with findings in young, normal women and in patients with certain menstrual disorders. A total of 50 complete menstrual cycles in 37 were examined. Five distinct patterns of hormonal regulation were found, three of which are reported here: (a) A long follicular phase and delayed follicular maturation in young women with long, unpredictable intermenstrual intervals from menarche; (b) a short follicular phase with increasing age and in short cycles in perimenopausal women; and (c) true anovulatory vaginal bleeding in long cycles in perimenopausal women. The short cycles before and during the menopausal transition were found to have lower E2 levels and high FSH concentrations throughout, while LH remained in the normal range. During long cycles in perimenopausal women, concentrations of LH and FSH were in the menopausal range. However, follicular maturation was observed months after high levels of gonadotropins were attained. These studies permit the characterization of the menstrual history of the normal woman in terms of the hormonal changes that occur and provide a basis for the definition of several disorders of follicular maturation.
521 citations
"Hormonal changes in the menopause t..." refers background in this paper
...A landmark study was performed by Sherman and Koren- man (1975), who reported on 50 complete menstrual cycles in 37 women....
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